Function of the exoribonuclease pacman in cell movement and cell shape change

伤口愈合需要周围的皮肤细胞拉伸、拉紧和密封，以覆盖皮肤细胞层的洞。这种伤口愈合的过程类似于所有胚胎发育过程中的其他细胞膜运动。我们已经证明，参与破坏信使RNA的一种酶对于果蝇黑腹果蝇的细胞膜封闭过程是必要的。这种名为Pacman的酶将这些信使RNA从一端咀嚼到另一端。信使RNA是指导细胞制造特定蛋白质的分子。我们已经发现，吃豆人很可能是一个庞大的蛋白质复合体的一部分，一个可以有效地摧毁或监禁信使RNA的死亡之星。我们怀疑，吃豆人必须破坏RNA，这可能会阻止细胞板的密封过程。这个项目的目的是找出吃豆人如何控制这个洞的关闭过程。控制机制可能涉及到针对特定的mRNAs进行破坏，我们将测试是否是这样的情况。虽然这个项目将使用果蝇进行，但它也与人类伤口愈合等上皮片封闭过程有关，因为两种生物的细胞过程令人惊讶地相似。此外，果蝇和人类的Pacman酶极其相似，因此我们在这个项目中获得的见解可能有助于我们改进伤口的治疗，也有助于我们了解胚胎中的细胞运动过程。这项提案中描述的工作也是针对在RNA水平上的基因调控的一般问题。最近人们认识到，通过使用RNA本身作为一种工具来拒绝特定的基因，可以在信使RNA的水平上控制基因。在一种称为RNA干扰的过程中，有可能下调细胞中任何特定的RNA。由于Pacman及其同系物已被证明与RNA干扰有关，该项目还将为将这一过程用于治疗目的的改进提供创新的见解。

Wound healing requires the surrounding skin cells to stretch, draw together and seal to cover the hole in the layer of skin cells. This process of wound healing is similar to other cell sheet movements in the development of all embryos. We have shown that an enzyme involved in the destruction of messenger RNAs is necessary for the cell sheet sealing process in the fruit fly Drosophila melanogaster. This enzyme, which is named Pacman, chews up these messenger RNAs from one end to the other. Messenger RNAs are the molecules which instruct the cell to make particular proteins. We have found out that Pacman is likely to be part of a large complex of proteins, a 'Death Star' which can efficiently destroy or imprison messenger RNAs. We suspect that Pacman must destroy RNAs that would potentially stop the cell sheet sealing process. The aim of this project is to find out how Pacman can control this hole closure process. The control mechanism probably involves targeting particular mRNAs for destruction by the 'Death Star' complex and we will test whether this is the case. Although this project will be carried out using the fruit fly Drosophila, it also has relevance for epithelial sheet sealing processes such as wound healing in humans as the cellular processes are surprisingly similar in both organisms. In addition, the Pacman enzyme is extremely similar between flies and humans therefore the insights we gain during this project may help us to improve the treatment for wounds and also help us to understand the cell movement process in embryos. The work described in this proposal is also directed towards the general question of gene regulation at the RNA level. It has recently become recognised that genes can be controlled at the level of the messenger RNA by using RNA itself as a tool to turn down specific genes. In a process termed RNA interference, it is possible to downregulate any particular RNA in the cell. Since Pacman and its homologues have been shown to be involved in RNA interference, this project will also may also provide innovative insights into the improval of this process for therapeutic purposes.